Disease relevance of Tropisteron

• Emesis was much better controlled with tropisetron than with standard drugs, complete control during the first 24 hours being achieved in 42% and 8% of patients, respectively, (p less than 0.001) [1].
• The two main adverse events in human volunteer tolerability studies with tropisetron were headache and constipation [2].
• Toxicological studies show that tropisetron is generally well tolerated by all animal species investigated and no specific organ toxicity was observed, other than slight loss of body weight development [2].
• Treatment of diarrhea in carcinoid syndrome with ondansetron, tropisetron, and clonidine [3].
• We evaluated the prophylactic effect of tropisetron on postoperative nausea and vomiting associated with epidural morphine [4].

Psychiatry related information on Tropisteron

• A randomized double-blind placebo-controlled study of tropisetron in the treatment of outpatients with generalized anxiety disorder [5].
• NAN-190, a 5-HT 1A receptor antagonist, (-)-pindolol, a 5-HT 1A/1B receptor antagonist, and tropisetron, a 5-HT(3/4) receptor antagonist, did not affect the pain threshold in the hyperalgesic hind limb to the same extent as in the normal hind limb [6].
• Moreover, 5,7-DHT lesions produced a tendency to increase motor activity in tropisetron-treated rats [7].
• Using measurements of rodent behaviour in the mouse light and dark test box and rat social interaction, anxiolytic agents such as diazepam and putative anxiolytic agents such as the 5-HT1A and 5-HT3 receptor ligands 8-OH-DPAT and low doses of tropisetron release behaviour suppressed by the aversive situation [8].
• Alcohol drinking in rats treated with 5,7-dihydroxytryptamine: effect of 8-OH-DPAT and tropisetron (ICS 205-930) [9].

High impact information on Tropisteron

• Adverse reaction to 5-HT3 antagonist ICS 205930 [10].
• The relationship between the CYP2D6 genotypes and the tropisetron serum concentrations 3 and 6 hours after drug administration was analyzed in a subgroup of 42 patients [11].
• These excitations had a latency of 36 +/- 4 ms and a duration of 69 +/- 9 ms and were blocked by the i.v. administration of the 5-HT3 receptor antagonists ondansetron and tropisetron [12].
• Thus, 5-HT(3) receptor antagonists block ACh-evoked currents in alpha 9 alpha 10-injected Xenopus laevis oocytes with a rank order of potency of tropisetron (IC(50), 70.1 +/- 0.9 nM) > ondansetron (IC(50), 0.6 +/- 0.1 microM) = MDL 72222 (IC(50), 0.7 +/- 0.1 microM) [13].
• In addition, 5-HT, PBG, and tropisetron were investigated through radioligand binding to isolated membranes [14].

Chemical compound and disease context of Tropisteron

• In all patients receiving cisplatin, the tropisetron/dexamethasone combination produced total control of acute emesis [15].
• Zatosetron and tropisetron significantly inhibited cisplatin-evoked emesis in dogs (estimated ID50 values of 34.4 +/- 2.3 micrograms/kg and 108.3 +/- 4.8 micrograms/kg i.v., respectively) [16].
• Pyrogallol (128 mg kg-1, i.p.)-induced emesis was prevented by treatment with MPG (i.p.) or tropisetron (s.c.) with ID50 values of 149 mg kg-1 and 117 micrograms kg-1, respectively [17].
• Copper sulfate-induced emesis in dogs was also prevented by FK1052, tropisetron, and CP-122,721 but not by ondansetron [18].
• Tropisetron inhibited 5-HT- and cholera toxin-induced effects at high dose but only diminished heat stable E. coli enterotoxin-induced effects [19].

Biological context of Tropisteron

• Chronic treatment of male and female Wistar rats with a 5-HT3 receptor antagonist, tropisetron (ICS; 5 mg/kg/day) or ondansetron (0.5 mg/kg/day), prevented or reversed psychosocial stress-induced increases in blood pressure in stressed rats with no significant effect on blood pressure of unstressed control rats [20].
• In microculture neurons, 5-HT transiently reduced action potential-evoked inhibitory autaptic currents by > 50%; this effect was blocked by tropisetron and mimicked by 20 mm, but not 10 mm, K(+) [21].
• Pharmacology, toxicology and human pharmacokinetics of tropisetron [2].
• The drug is extensively metabolized in man, with the enzymes involved in tropisetron biotransformation being unknown [22].
• The two highest doses of tropisetron partially attenuated a significant decrease in water intake produced by morphine (17.0 mg/kg) [23].

Anatomical context of Tropisteron

• Since T cells play a key role in the onset of several inflammatory diseases, we have evaluated the immunosuppressive activity of tropisetron in human T cells, discovering that this compound is a potent inhibitor of early and late events in TCR-mediated T cell activation [24].
• Intracisternal administration of tropisetron decreased the orofacial nocifensive behavior in the late phase evoked by the injection of formalin into the masseter muscle [25].
• 7 Tropisetron (10 microM), SDZ 205-557 (3 microM) and GR 113808 (10-100 nM) caused an increase in basal tone of the rat terminal ileum when administered in the presence of methysergide and atropine [26].
• Injection of tropisetron (0.005 and 0.01 microgram) or ondansetron (1.0 and 2.5 micrograms) into the hippocampus increased punished consumption of water in the Vogel conflict test [7].
• The 5-HT(3) receptor-specific antagonist tropisetron blocked only the mCPBG-induced responses, but not the nicotinic responses on the same synaptosomes [27].

Associations of Tropisteron with other chemical compounds

• PATIENTS AND METHODS: We applied a novel statistical approach to investigate whether the efficacy of the 5HT3 receptor antagonist ICS 205-930 (tropisetron) is maintained over repeated cycles of weekly high-dose cisplatin [28].
• Most comparative studies showed tropisetron monotherapy to be more effective than metoclopramide in controlling acute nausea and vomiting, with the exception of 1 study which showed similar efficacy [29].
• The 5-HT3/4 antagonist tropisetron (ICS 205-930) or 5-HT3 antagonist granisetron abolished luminal stimuli-evoked nodose neuronal responses [30].
• Two dosages (5 mg and 25 mg) of the selective 5HT3 receptor antagonist tropisetron (ICS 205-930) were administered to healthy male controls, and the effects on the sleep EEG and nocturnal secretory activity of growth hormone (GH) and cortisol were evaluated [31].
• Efficacy and tolerability of tropisetron in comparison with a combination of tropisetron and dexamethasone in the control of nausea and vomiting induced by cisplatin-containing chemotherapy [32].

Gene context of Tropisteron

• Enzyme kinetics for formation of 5-hydroxy (5-OH-ICS), 6-hydroxy (6-OH-ICS) and N-demethyl tropisetron (N-De-ICS) were studied in the microsomal fraction of eight human livers (seven livers from extensive metabolizer (EM), one liver from a poor metabolizer (PM) for CYP2D6) [22].
• Because these are the major pathways in vivo, coadministration of drugs competing for CYP2D6 and possibly CYP3A4 could influence the human kinetics of tropisetron and ondansetron [33].
• In conclusion, our data show that the binding of tropisetron to 5-HT3 receptors results in antiinflammatory effects through inhibition of TNF-alpha/IL-1beta, which might explain the antiphlogistic effects of 5-HT3 antagonists [34].
• Furthermore, pretreatment with 5-HT2A receptor antagonist (ketanserin), but not with 5-HT3 receptor antagonist (tropisetron), attenuated the behavioral response after the injection of 5-HT [35].
• In order to assess the effect of antagonizing 5-HT2A or 5-HT3 receptors on formalin-induced Fos-LI, rats were pre-treated with local (masseter muscle) administration of ketanserin or tropisetron (0.01, 0.1 mg/rat) 20 min prior to formalin injection [36].

Analytical, diagnostic and therapeutic context of Tropisteron

• PATIENTS AND METHODS: One thousand seventy-two patients, who were scheduled to receive at least two identical cycles of emetogenic chemotherapy, were treated with 5 mg tropisetron once daily in their first chemotherapy course [37].
• METHODS: Twenty-six rapid metabolizers of tropisetron were included in this double-blind crossover study [38].
• Tropisetron seems to be a promising and well tolerated drug in conjunction with extended radiotherapy of abdominal fields [39].
• In a multicentre trial, 78 patients with a variety of malignancies, who had experienced insufficient control of emesis (greater than or equal to 3 episodes within 24 hours) while receiving standard antiemetics during previous chemotherapy, were randomly assigned to receive tropisetron 5mg once daily for 5 days or conventional antiemetic drugs [1].
• Effects of 5HT3 receptor antagonism by tropisetron on the sleep EEG and on nocturnal hormone secretion [31].

References